Coenzyme Q10 (CoQ10) is also known as ubiquinone or ubidecarenone, and its chemical name is 2,3-dimethoxy-5-methyl-6-decaprenyl benzoquinone. The biological activity of coenzyme Q10 comes from the oxidation-reduction properties of the quinone ring thereof and the physicochemical properties of the side chain thereof. Coenzyme Q10 is a natural antioxidant and cell metabolism activator produced by a cell per se, and it has functions such as anti-oxidation property, eliminating free radicals, improving immunity of the body, anti-aging, etc. Clinically, it is widely applied in the treatment of various diseases such as heart diseases, cancers, diabetes, acute and chronic hepatitis, and Parkinson's disease, and it also has broad applications in foods, cosmetics, and anti-aging health products.
At present, microbial fermentation is the major way to produce coenzyme Q10. The production of coenzyme Q10 by microbial fermentation has great competitive advantages in terms of both product quality and safety, and is suitable for large-scale industrial production.
The fermentation stage of microbiological production of coenzyme Q10 is generally divided into the following two stages: 1) a bacterial growth stage (also known as a microbial growth and reproduction stage), in which stage, it is generally necessary to maintain sufficient oxygen supply and nutrition so that microorganisms rapidly grow and reproduce to reach the bacterial concentration required for production, and meanwhile, the synthesis of the metabolite coenzyme Q10 starts quickly; 2) a coenzyme Q10 synthesis and accumulation stage (sometimes also referred to as a synthesis stage), at which stage, the fermentative bacteria rapidly consume oxygen, the dissolved oxygen in a fermentation broth is usually at a low level, and the fermentative microorganisms are in an oxygen-limited state, during which time the metabolite coenzyme Q10 is quickly synthesized and accumulated. The synthesis and accumulation stage is usually divided, based on the changes in the potency of coenzyme Q10 in the fermentation broth, into an early phase (the potency of coenzyme Q10 maintains a steep ascendant growth curve), a middle phase (the growth curve of the potency of coenzyme Q10 slows down, but the potency still maintains a significant growing trend) and a late phase (the growth curve of the potency of coenzyme Q10 tends to be steady, and the potency slightly increases along with the fermentation time). In general, the time interval between the early, the middle, and the late phases of the coenzyme Q10 synthesis and accumulation stage is about 10 to 20 hours.
As disclosed in CN102876743B, the fermentation process is regulated by a phased oxygen supply control strategy: a high oxygen supply is adopted in the bacterial growth stage and the early phase of the synthesis and accumulation stage of the fermentation process to promote rapid growth of the bacteria and quick start of coenzyme Q10 synthesis; after bacterial growth enters a stable phase (the bacteria no longer exhibit a significant net increase), the oxygen supply is reduced in phases to maintain a high coenzyme Q10 specific production rate and decrease the consumption of the substrate glucose. Such a phased change of oxygen supply mode may result in best physiological property status of the production bacteria and reduce the cost of coenzyme Q10 production.
In the process of producing coenzyme Q10 by microbial fermentation, those skilled in the art usually achieve the goal of high yields of coenzyme Q10 by adjusting influence factors such as the strain, the dissolved oxygen, the temperature, the pressure, the medium, and the nutrient feeding rate in the fermentation broth. For example, patent CN105420417A proposes that the fermentation process of coenzyme Q10 is controlled synergistically by adjusting the oxygen consumption rate (dissolved oxygen) and conductivity (nutrient feeding rate); while patent CN104561154A adjusts process parameters by using the shape of the bacteria in the fermentation process as a criterion; patent CN103509729B modifies Rhodobacter sphaeroides to improve its ability to synthesize coenzyme Q10. The common feature of these processes is that the produced coenzyme Q10 is a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10, and the proportion of the reduced coenzyme Q10 is relatively high. In particular, in the process described in U.S. Pat. No. 7,910,340B2, after fermentation is completed, the content of reduced coenzyme Q10 in the coenzyme Q10 produced by microorganisms is 70% or more.
Since oxidized coenzyme Q10 and reduced coenzyme Q10 can be converted to each other in cells, either type of coenzyme Q10 can function as an electron transporter and perform relevant physiological functions. Moreover, because oxidized coenzyme Q10 is relatively stable and easier to preserve, there has been an increasing market demand for oxidized coenzyme Q10 in recent years.
None of the aforementioned patents CN105420417A, CN104561154A, CN103509729B reports any special treatment of the coenzyme Q10 produced by microorganisms to convert reduced coenzyme Q10 into oxidized coenzyme Q10. Although the U.S. Pat. No. 7,910,340B2 proposes that an oxidation means can be adopted in a post-treatment process to convert most of reduced coenzyme Q10 into oxidized coenzyme Q10, the post-treatment process is complicated and its cost is high. There is also no report in the prior art on a method for directly producing high-content oxidized coenzyme Q10 with microbial fermentation.